This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Melatonin is a vertebrate hormone that plays numerous roles in circadian timing of a variety of metabolic processes. Recent studies in rat neuroblastoma cells show both a neuritogenic and a neuroprotective influence of melatonin. Previous studies have shown that melatonin may have phylogenetically-conserved roles in crustacean physiology. We are studying a crustacean cell subtype, the x-organ cell, that is multipolar and shows rapid neurite outgrowth and arborization in culture. Unlike the well-studied neuroblastoma cells, crustacean cells are highly differentiated and are neurosecretory;they are analogous to vertebrate hypothalamic neurosecretory cells. The growth patterns and activities of these cells, and their ease of culture, provide a model system for the roles of melatonin in a variety of cell activities. Our current studies have shown that melatonin enhances neurite growth in these cells in a dose-dependent and potentially receptor-mediated manner. Furthermore, melatonin plays a protective role in response to exposure of the cells to growth-inhibiting but nonlethal levels of hydrogen peroxide. Immunocytochemistry indicates melatonin receptor-like binding on these cells, and prior work in my laboratory has shown that melatonin likely induces the release of neuropeptides from these cells. We are currently studying these receptors and are exploring the cellular and molecular effects of melatonin on the neurosecretory and neuritogenic activities of x-organ cells.